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Articles 1 - 7 of 7
Full-Text Articles in Life Sciences
Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla
Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla
Electronic Thesis and Dissertation Repository
Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this thesis was …
Identification Of A Novel Interaction Between Integrin-Linked Kinase And Beta-Arrestin 1, Hannah E. Murphy-Marshman
Identification Of A Novel Interaction Between Integrin-Linked Kinase And Beta-Arrestin 1, Hannah E. Murphy-Marshman
Electronic Thesis and Dissertation Repository
Integrin-linked kinase (ILK) is a ubiquitous scaffold protein essential for the development of front-rear polarity and directional migration of epidermal keratinocytes. β-arrestin 1 is another adaptor protein which has recently emerged as a key factor in modulating proliferation and migration of various cell types. Previous studies have demonstrated an association between β-arrestin 2 and ILK in cerebellar granule precursor cells. I have now identified a novel interaction between ILK and β-arrestin 1 in primary keratinocytes that occurs directly and without post-translational modifications. The N-terminal 67 residues of ILK and multiple regions in β-arrestin 1 are important for this interaction. This …
The Role Of Gaba Signalling In Lung Macrophage Immune Response, Jacob W. Poirier
The Role Of Gaba Signalling In Lung Macrophage Immune Response, Jacob W. Poirier
Electronic Thesis and Dissertation Repository
Lung macrophages (LMϕs) play a key role in pulmonary innate immunity. They polarize into different phenotypes adapting to the needs of the immediate pulmonary environment. Studies in our laboratory suggest that murine LMϕs are endowed with an autocrine gamma-aminobutyric acid (GABA) signaling system. My honors thesis study found that antagonizing the autocrine GABA signaling in alveolar macrophages (AMϕs) increased secretion of the M1 cytokine tumor necrosis factor-alpha (TNF-α), suggesting a role for GABA signaling in immune response. This project explored whether GABA signaling plays a role in LMϕ polarization. Results from this study confirmed that bacterial toxin lipopolysaccharide (LPS) and …
Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad
Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad
Electronic Thesis and Dissertation Repository
PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the CRFR1 PDZ-binding motif. …
Glycosylation On Stromal Interaction Molecule-1 Ca2+ Sensing Region Enhances Store Operated Ca2+ Entry, Yoo Jung Choi
Glycosylation On Stromal Interaction Molecule-1 Ca2+ Sensing Region Enhances Store Operated Ca2+ Entry, Yoo Jung Choi
Electronic Thesis and Dissertation Repository
A major intracellular calcium (Ca2+) uptake pathway in excitable and non-excitable eukaryotic cells is store-operated Ca2+ entry (SOCE). Stromal interaction molecule-1 (STIM1) is the key regulator of SOCE and responds to changes in endoplasmic reticulum (ER)-stored Ca2+ through luminal sensing machinery composed of EF-hand and SAM domains (EFSAM). EFSAM can undergo N-glycosylation at Asn131 and Asn171 sites; however, the exact molecular and functional effects of N-glycosylation are unclear. By establishing a site-specific chemical approach to covalently linking glucose to EFSAM and subsequently examining EFSAM biophysical properties, I found that this modification enhances STIM1 activation …
Cardiovascular Characterization Of Cx40/Panx1 Single And Double Knockout Mice, Meghan L. Jelen
Cardiovascular Characterization Of Cx40/Panx1 Single And Double Knockout Mice, Meghan L. Jelen
Electronic Thesis and Dissertation Repository
Connexins (Cxs) and pannexins (Panxs) are protein families that form large-pore channels which exist at the plasma membrane for both intracellular and extracellular signaling. Given their potential for overlapping cellular signaling functions we proposed that mice lacking both a connexin and a pannexin would have a severe phenotype. To investigate this possibility we crossed Panx1 null mice with Cx40 knockout mice and characterized the first global connexin/pannexin double knockout mouse. Intriguingly, the combined ablation of both Cx40 and Panx1 caused decreased prenatal and newborn survival, but did not affect the fertility or lifespan of surviving mice. Cx40-/- and Cx40 …
Putative Pore-Lining Residues And Intracellular Magnesium Influence Connexin50 Unitary Gap Junction Channel Conductance, Swathy Sudhakar
Putative Pore-Lining Residues And Intracellular Magnesium Influence Connexin50 Unitary Gap Junction Channel Conductance, Swathy Sudhakar
Electronic Thesis and Dissertation Repository
Gap junction channels (GJs) are oligomers of connexins forming channels linking neighbouring cells. GJs formed by different connexins show distinct unitary channel conductance (γj), transjunctional-voltage dependent gating (Vj-gating) properties, and magnesium modulation. We investigate here how pore-lining residues may influence these GJ properties. We mutated putative pore-lining residues in Cx50 GJ (G8E/G46E/V53E individually or in combination) to investigate γj, Vj-gating, and magnesium modulation. GJs formed by combination mutants (G8E-G46E, G46E-V53E, and G8E-G46E-V53E) were functional and showed a significantly increased γj with little change in Vj-gating, while G8E-V53E mutants failed …